Diabetes is classified into type I diabetes and Type II diabetes according to its dependence on insulin. Insulin dependent type I diabetes, which is dominant among diabetes, is developed by destruction of beta cells of pancreas that produce insulin, indicating that insulin is not generated in vivo. In the case of insulin resistant type II diabetes, insulin generation in pancreas is normal but insulin is not functioning in peripheral organs, which causes the disease (1).
Insulin resistance in muscle which is the main tissue to eliminate glucose and fatty acid indicates that type II diabetes is beginning. Type II diabetes is aging-dependent disease. thus, the incidence rate of type II diabetes increases as aging progresses (2). In general, type II diabetes, taking 70-80% of entire diabetes, exhibits the symptom of obesity as it progresses. However, in Asia, particularly in Korea, only 20-30% of type II diabetes patients are obese and most of the patients are not obese (3).
In the meantime, it has not been explained yet what kind of role the aging plays in type II diabetes which is age-dependent but does not exhibit the symptom of obesity. It might be one reason that a proper diabetes model has not been established.
For diabetes study, animal models such as rats have been used for clinical tests, precisely ob/ob mice or OLETF rats characterized by having diabetes with the symptom of obesity when they are young are the examples (4, 5). Recently, US patent No. 2007/012487 describes the animal model for human type II diabetes produced by mating a C57BL/6 mouse and a DBA/2 mouse, which is expected to contribute greatly to studies on the treatment and improvement of type II diabetes.
Caveolaeis the intracellular invagination of 50-100 nm in size which contains 21-24 kDa structural protein called caveolin (6). Caveolin is largely divided into three groups: caveolin-1, caveolin-2 and caveolin-3. Caveolin-1 and caveolin-2 are commonly expressed in many kinds of cells and form hetero oligomer in cell membrane. In the meantime, caveolin-3 is expressed specifically in skeletal muscles and regulates muscle fiber generation (8). It has been recently reported that caveolin-1 plays an important role in regulating glucose homeostasis in adipocytes (9, 10). It has also been reported by the present inventors that caveolin-1 plays an important role in senescent phenotype (11, 12) and caveolin-1 is expressed more in aged rat tissues than in young rat tissues (13). According to the previous reports, caveolin-1 is expressed in muscle tissue (14-16), and binds to caveolin-3 specifically in muscle tissue (17). The present inventors investigated functional importance of caveolin-1 and caveolin-3 in muscle tissues. As a result, the present inventors found out that it was not caveolin-3 but caveolin-1 that played an important role in glucose absorption in differentiated muscle cells (18).
Many of patent descriptions and papers are cited in this description and presented by brackets. The cited patent descriptions and papers are attached herein as references and help clear understanding of arts and context of this patent.